cagrilintide/semaglutide (CagriSema) / Novo Nordisk - LARVOL DELTA

Novo Nordisk today announced topline result from the phase 3…REDEFINE 9 trial of once-weekly CagriSema (cagrilintide and semaglutide), an investigational product, and Novo’s next innovation in weight management and type 2 diabetes. (GlobeNewswire) - "In REDEFINE 9, CagriSema 1.0 mg/1.0 mg provided a weight reduction of 21.0% versus 2.0% for placebo, and the primary superiority endpoint was met. CagriSema also showed greater improvements than placebo across prespecified supportive endpoints, including systolic blood pressure, waist-to-height ratio and fasting lipid profile." "

P3 data: top line • Obesity • Type 2 Diabetes Mellitus

Novo’s CagriSema delivers superior weight loss versus tirzepatide in REIMAGINE 5 trial (GlobeNewswire) - "In REIMAGINE 5, CagriSema 1.0 mg/1.0 mg was superior to tirzepatide 5 mg for weight loss, achieving an estimated average weight loss of 12.4%, compared with 9.1%, respectively. CagriSema also confirmed non-inferior reduction in HbA1c (1.71%) versus tirzepatide (1.67%)."

P3 data: top line • Obesity • Type 2 Diabetes Mellitus

Efficacy and Safety of CagriSema for Metabolic Outcomes: Systematic Review and Pairwise Meta-Analysis of Randomized Controlled Trials. (PubMed, Diabetes Metab Syndr Obes) - "To evaluate the efficacy and safety of dual-agonist CagriSema vs semaglutide monotherapy, cagrilintide monotherapy, and placebo in adults with overweight/obese status and type 2 diabetes, we searched Embase, MEDLINE, PubMed, and the Cochrane Library up to 14 June 2026 for randomized controlled trials (RCTs)...Compared with current standard monotherapies and placebos, CagriSema demonstrates superior weight loss, glucose, and lipid control. Key limitations include the relatively small number of eligible trials and the current lack of long-term cardiovascular endpoints."

Journal • Retrospective data • Cardiovascular • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • CRP

Effect of CagriSema According to Baseline BMI and Obesity-Related Complications: REDEFINE 1 Trial (OBESITY WEEK 2026) - No abstract available

Genetic Disorders • Obesity

A novel unimolecular tetra-agonist peptide targeting GLP-1, GIP, amylin and calcitonin receptors produces superior weight loss efficacy and quality than tirzepatide or CagriSema in obese rats (EASD 2026) - "Materials and DIO rats received PTT-A (10 or 30 nmol/kg), tirzepatide (30 nmol/kg), or CagriSema (2 nmol/kg cagrilintide plus 2 nmol/kg semaglutide) for 21 days... PTT-A achieves greater and more selective weight loss than tirzepatide or CagriSema, driven by enhanced fat loss and lean mass preservation. These findings highlight our tetra-agonism approach as a promising next generation therapy for treating obesity and its metabolic complications, with the potential for sustained efficacy and acceptable safety."

Preclinical • Metabolic Disorders • Obesity

A frequentist network meta-analysis of bariatric surgery versus next-generation injectable and oral incretins for cardiometabolic disease (EASD 2026) - "Materials and A frequentist network meta-analysis was conducted synthesizing data from surgical RCTs (Roux-en-Y Gastric Bypass [RYGB], Sleeve Gastrectomy [SG]) and Phase 2/3 trials of advanced pharmacotherapies (tirzepatide, retatrutide, survodutide, CagriSema, and orforglipron)... When pooling estimates across broad metabolic populations, next-generation incretins successfully bridge the placebo- adjusted efficacy gap to bariatric surgery. The most potent injectable multi-agonists match the absolute mass offloading of sleeve gastrectomy, while accessible daily oral small molecules rival legacy surgical banding."

Bariatric surgery • Retrospective data • Surgery • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Research Study on How People With Type 2 Diabetes Tolerate Switching From Semaglutide to Cagrisema (clinicaltrials.gov) - P3 | N=210 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P3 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Current and forthcoming pharmacotherapies for adolescent obesity: Evidence-based review. (PubMed, World J Clin Pediatr) - "It is more effective than liraglutide in improving insulin sensitivity...Although no short-term safety issues have been reported, there is still little information available on Tirzepatide and CagriSema in adolescents, compared to their known effect on adults. Therefore, we conclude that semaglutide is the current gold standard, but that there is an urgent need for longer-term studies, comparative evaluations, and safety trials that include paediatric cohorts in order to ensure safe access to pharmacological innovations."

Journal • Review • Cardiovascular • Genetic Disorders • Heart Failure • Metabolic Disorders • Obesity • Pediatrics

REIMAGINEYOUNG: A Research Study to See How Much CagriSema Lowers Blood Sugar and Body Weight Compared to Placebo in Children and Adolescents With Type 2 Diabetes (clinicaltrials.gov) - P3 | N=80 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • LEP • LEPR

A Research Study to Investigate the Effects of CagriSema Compared to Placebo in People With Type 2 Diabetes and Painful Diabetic Peripheral Neuropathy (clinicaltrials.gov) - P2 | N=142 | Completed | Sponsor: Novo Nordisk A/S | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Diabetic Neuropathy • Metabolic Disorders • Peripheral Neuropathic Pain • Type 2 Diabetes Mellitus

Novo to share real-world and clinical data including Wegovy pill, and cardiometabolic pipeline progress with next-generation amylin treatments at EASD 2026 (GlobeNewswire) - "New data will highlight the breadth of semaglutide evidence across the cardiometabolic spectrum, including obesity, type 2 diabetes, cardiovascular, kidney and fatty liver disease, and new data on Wegovy pill, Wegovy 7.2 mg and Ozempic 2.0 mg. Real-world evidence from the OCTANE study will provide insights into Wegovy pill use in adults with overweight or obesity, including weight outcomes, treatment switching and patient-reported outcomes. CagriSema and amylin-based pipeline data will provide new insights into appetite regulation, eating behaviour, food noise, body composition and bone health (bone remodelling mechanisms). The data will advance our understanding of the underlying biology of obesity and type 2 diabetes and inform next-generation cardiometabolic innovation."

Clinical data • Cardiovascular • Obesity • Type 2 Diabetes Mellitus

Pharmacological management of obesity: Current landscape and emerging therapies. (PubMed, Indian J Pharmacol) - "Currently, six medications (Orlistat, Phentermine/Topiramate, Naltrexone/Bupropion, Liraglutide, Semaglutide, and Tirzepatide) are approved by the U.S. Food and Drug Administration for long-term obesity management and among these, glucagon-like peptide receptor agonists have revolutionized the therapy...It has new dual and triple combinations such as CagriSema, Survodutide, and Retatrutide for better efficacy and metabolic outcomes, as well as long-acting and oral formulations, which will improve adherence and accessibility. India released its new obesity guideline in January 2025, emphasizing on early pharmacotherapy initiation and the adoption of stage-based obesity classification. Together, these developments signify a transformative era in obesity care where pharmacotherapy is a powerful and evidence-based tool that, in many cases, approaches the efficacy and metabolic benefits traditionally associated with bariatric surgeries."

Journal • Review • Cardiovascular • CNS Disorders • Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Obesity • Psychiatry • Type 2 Diabetes Mellitus

Effects of CagriSema on Physical and Psychosocial Function in Overweight or Obesity: REDEFINE 1 (OBESITY WEEK 2026) - No abstract available

Genetic Disorders • Obesity

Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonists and Co-agonists for Weight Loss Among Adults Without Diabetes : An Updated Systematic Review. (PubMed, Ann Intern Med) - "To update our prior systematic review evaluating the efficacy and safety of GLP-1 RAs and co-agonists among adults with overweight or obesity without diabetes...Among commercially available therapies, placebo-subtracted weight loss reached up to -5.8% (95% CI, -8.0% to -3.6%) for liraglutide, -14.8% (CI, -16.2% to -13.4%) for subcutaneous semaglutide, -14.3% (CI, -17.2% to -11.4%) for oral semaglutide, -12.4% (CI, -15.1% to -9.7%) for orforglipron, and -19.0% (CI, -21.6% to -16.4%) for tirzepatide. Numerically greater placebo-subtracted reductions were seen with emerging multiagonists, including -23.9% (CI, -29.3% to -18.5%) with amycretin and -22.1% (CI, -24.9% to -19.3%) with retatrutide...Head-to-head data showed greater weight loss with semaglutide and JNJ-64565111 than liraglutide and greater weight loss with tirzepatide and cagrilintide-semaglutide (CagriSema; Novo Nordisk) than semaglutide...None. (PROSPERO: CRD42024505558)."

Journal • Review • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity

Comparative efficacy and safety of glucagon-like peptide 1 based drugs for weight loss in adults with overweight or obesity without diabetes: network meta-analysis of randomised controlled trials. (PubMed, BMJ Med) - "Compared with placebo, weight loss was greatest with retatrutide (-22.10%, 95% confidence interval -25.60% to -18.60%), followed by tirzepatide (-19.28%, -20.39% to -18.16%), and CagriSema (a combination of cagrilintide and semaglutide, -17.32%, -19.32% to -15.32%)...Low certainty evidence suggested higher rates for discontinuing treatment with danuglipron and retatrutide, whereas mazdutide showed better tolerability...Differences in tolerability, limited head-to-head evidence, and residual uncertainty, however, should be considered when interpreting comparative treatment effects. PROSPERO CRD420261279841."

Journal • Retrospective data • Diabetes • Endocrine Disorders • Genetic Disorders • Metabolic Disorders • Obesity

A Study to See How Metabolism is Influenced by Weight Loss Due to Intervention With Cagrilintide and Semaglutide Compared to Diet (clinicaltrials.gov) - P1 | N=80 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2027 ➔ Feb 2028

Enrollment closed • Trial completion date • Genetic Disorders • Obesity

Effect of CagriSema on continuous glucose monitoring in people with inadequately controlled type 2 diabetes: REIMAGINE 2 (EASD 2026) - P3 | "Clinical Trial Registration Number: NCT06065540 Background and aims: In REIMAGINE 2, CagriSema, a fixed-dose cagrilintide and semaglutide combination, significantly reduced HbA 1c and body weight (BW) vs its monocomponents in people with type 2 diabetes (T2D) inadequately controlled on metformin ± sodium- glucose cotransporter-2 inhibitor, and overweight/obesity. CagriSema 2.4 mg/2.4 mg and semaglutide 2.4 mg led to clinically relevant improvements in TIR, TITR, PPG curves and TtN. Improvements with CagriSema 2.4 mg/2.4 mg were greatest in people with BL BMI ≥35 kg/m 2; semaglutide 2.4 mg efficacy was consistent regardless of BL BMI. These data support this combination therapy for improved glucose control, especially in people with BMI ≥35 kg/m 2 ."

Late-breaking abstract • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Effect of CagriSema on bone biomarkers in participants with inadequately controlled type 2 diabetes: REIMAGINE 2 (EASD 2026) - P3 | "Treatment with CagriSema, a fixed-dose combination of cagrilintide and semaglutide, leads to substantial weight loss in people with T2D (14.2% weight reduction with CagriSema 2.4 mg/2.4 mg at week 68 in the REIMAGINE 2 trial). CagriSema was associated with changes in CTX-1 and P1NP, that are consistent with reactivation of bone remodelling, in this population with T2D. Even with the substantial weight reduction observed with CagriSema, the stabilisation of CTX-1, coupled with the increase in P1NP from week 20 to 68 provides preliminary reassurance regarding bone changes with CagriSema in T2D."

Biomarker • Late-breaking abstract • Diabetes • Metabolic Disorders • Osteoporosis • Type 2 Diabetes Mellitus

Effect of CagriSema on achievement of composite HbA1c and body weight reduction targets in participants with type 2 diabetes: REIMAGINE 1 (EASD 2026) - P3 | "CagriSema demonstrated concurrent achievement of stringent glycaemic and BW reduction targets, which are associated with improvements in overall cardiometabolic health, and hence provides further evidence confirming the potential of CagriSema as an early intervention for individuals with T2D."

Late-breaking abstract • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy of CagriSema on body composition in participants with early type 2 diabetes: REIMAGINE 1 (EASD 2026) - P3 | "Weight reduction with CagriSema produced significant decreases in abdominal fat volume and organ fat accumulation, and significantly reduced thigh muscle fat content in the MRI sub-study of REIMAGINE 1, which may contribute to its overall disease- modifying metabolic benefits."

Clinical • Late-breaking abstract • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

CagriSema in focus: connecting phase 3 evidence across obesity and T2D (EASD 2026) - "Sponsored by Novo Nordisk A/S"

P3 data • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

CagriSema: releasing the power of amylin in obesity and T2D (EASD 2026) - "Sponsored by Novo Nordisk A/S"

Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Agonism of amylin and calcitonin receptors via cagrilintide, CagriSema and zenagamtide are beneficial for bone health in a rat model of ovariectomy-induced osteoporosis (EASD 2026) - "Alendronate (10 ug/kg) and sham operated animals served as a positive and healthy controls, respectively...Weight matching by energy restriction reduced bone formation, as reflected by P1NP levels, compared to vehicle and this decrease was ameliorated after treatment with cagrilintide, semaglutide, CagriSema or zenagamtide (p<0.05) suggesting an overall net- beneficial effect on bone turnover... Cagrilintide, CagriSema, and zenagamtide ameliorated bone loss and structural deterioration in OVX rats. This was not observed to a similar extent with the GLP1R agonist semaglutide, thereby, suggesting a uniquely beneficial effects of these AMYR/CTR agonists for bone health. Thus, such amylin agonist may promote a healthier weight loss in patients by mitigating bone loss."

Preclinical • Metabolic Disorders • Obesity • Osteoporosis • COL1A2

Impact of cagrilintide 2.4 mg on physical function: post-hoc patient-reported outcomes from REDEFINE 1 (EASD 2026) - P3 | "Materials and REDEFINE 1 was a phase 3 trial that randomised (21:3:3:7) adults without diabetes and with BMI ≥30 kg/m 2 or ≥27 kg/m 2 and at least one obesity-related complication to CagriSema 2.4 mg/2.4 mg, semaglutide 2.4 mg, cagrilintide 2.4 mg, or placebo for 68 weeks... Cagrilintide 2.4 mg monotherapy improved physical function in people with overweight or obesity."

Clinical • Patient reported outcomes • Retrospective data • Diabetes • Metabolic Disorders • Obesity

Relationship between mean CagriSema dose and weight loss in the REDEFINE 1 trial (EASD 2026) - P3 | "Materials and In the phase 3 REDEFINE 1 trial, 3417 adults with a BMI ≥30 kg/m 2 , or ≥27 kg/m 2 with ≥1 obesity-related complication, were randomised 21:3:3:7 to receive once-weekly CagriSema (n=2108), semaglutide (n=302), cagrilintide (n=302) or placebo (n=705)... Substantial, clinically relevant weight losses were observed across all dose groups of CagriSema. The lack of a clear linear relationship between mean dose administered and relative weight loss indicates heterogeneity in effect, with some participants highly responsive to submaximal doses."

Metabolic Disorders • Obesity